1. Field of the Invention
The present invention relates to a method for converting pachymic acid and/or dehydropachymic acid in a material into tumulosic acid, dehydrotumulosic acid, polyporenic acid C and/or 3-epi-dehydrotumulosic acid effectively, so as to provide a product which is substantially free of pachymic acid and dehydropachymic acid. The product thus obtained can be further processed to provide a K2 composition that is enriched with tumulosic acid, dehydrotumulosic acid, polyporenic acid C and/or 3-epi-dehydrotumulosic acid. The aforementioned product and K2 composition can be used for treating cancers, in particular, for treating lung cancer.
2. Description of the Related Art
Researches have proven that triterpenoids such as pachymic acid, dehydropachymic acid, tumulosic acid, dehydrotumulosic acid, polyporenic acid C, and 3-epi-dehydrotumulosic acid are effective in such as diuresis, anti-oxidation, anti-cancer, anti-inflammation, anti-hyperglycemia, and immunoregulation. Although the triterpenoids have great efficacy and are potential in disease treatments, so far it is hard to synthesize the triterpenoids and their preparation methods are still unavailable. The triterpenoids currently used in industry are primarily obtained from the extract of FU-LING (Poria cocos) and/or the metabolic products of FU-LING, and it is hard to obtain the triterpenoids from other plants or fungi and the fermentation products thereof.
The research results have proven that, as compared to other triterpenoids of FU-LING, pachymic acid and dehydropachymic acid in the extract of FU-LING are less soluble in water, and this characteristic causes a great inconvenience to their application on disease treatments. For example, after administering a drug or a FU-LING extract that contains pachymic acid and/or dehydropachymic acid to a subject, the poor solubility of pachymic acid and dehydropachymic acid may adversely affect the treatment and control of diseases, and this is a task in this field extremely desired to be solved. Relevant description can be seen in such as “Absorption and transport of pachymic acid in the human intestinal cell line Caco-2 monolayers. Journal of Chinese integrative medicine. 6:704-710 (2008)”, which is entirely incorporated hereinto by reference.
In addition, the amounts of and proportion among pachymic acid, dehydropachymic acid, tumulosic acid, dehydrotumulosic acid, polyporenic acid C and 3-epi-dehydrotumulosic acid in a FU-LING medicinal material depend on the conditions such as growth environment, weather, and soil for planting the FU-LING, and this causes the combination of triterpenoids in FU-LING medicinal materials from different habitats/batches unstable and renders FU-LING medicinal materials not suitable for therapeutic purposes. Accordingly, for the application of the aforementioned triterpenoids in disease treatments, how to lead a subject after being administered with triterpenoids to acquire a stable amount of active ingredient is another task in this field extremely desired to be solved.
Furthermore, the manufacture of a triterpenoid medicament that contains tumulosic acid, dehydrotumulosic acid, polyporenic acid C and 3-epi-dehydrotumulosic acid only may meet the requirements of manufacturing a medicament with consistent components, reproducibility, consistent quantity, and quality control, and the inventors have found that this could be achieved by converting pachymic acid and dehydropachymic acid into tumulosic acid, dehydrotumulosic acid, polyporenic acid C and 3-epi-dehydrotumulosic acid to provide consistent components (various pre-experiments have proven that the proportion of components is approximately consistent). The present invention is directed to the discovery and also directed to the therapeutic effects of the converted products.
China Patent Application No. 00119304.X (Inventors: Dr. Xu Jin, etc.) alleges that an extract with triterpenoids at a content more than 70 wt % can be provided by organic extracting and alkalizing FU-LING However, the inventors of the present invention repeated the experiments of the said Chinese patent application and the results revealed that the real content of triterpenes is merely about 40%. It is believed that the inaccurate analysis results of China Patent Application No. 00119304.X (Inventors: Dr. Xu Jin, etc.) are resulted from the use of oleanolic acid color reaction analysis as the examination method. On the other hand, the inventors of the present invention adopted a FU-LING triterpene standards examination method to examine the content of triterpenoids. Furthermore, the inventors of the present invention found that the extraction and alkalization process of China Patent Application No. 00119304.X could not provide a FU-LING extract with a content of triterpenes over 50% because of the presence of phospholipids in FU-LING. On the other hand, the present invention comprises conducting a saponification process after the organic extraction process, this operation removes phospholipids and leads the content of triterpenoids to be more than 50% and to suitable for therapeutic purposes.
The present invention is directed to the results of the research for the above requirements. The inventors of the present invention found a method for providing a product that is substantially free of K1, and the product can be further processed to provide a K2-enriched composition to achieve the purposes of enriching K2 and meet the requirements of manufacturing a medicament with consistent components, reproducibility, consistent quantity, and quality control, thereby solving the aforementioned tasks effectively, wherein the K1 is at least one of pachymic acid and dehydropachymic acid, and the K2 is at least one of tumulosic acid, dehydrotumulosic acid, polyporenic acid C and 3-epi-dehydrotumulosic acid.